When people are confronted by an everyday, crowded visual scene, attentional mechanisms are needed to restrict visual processing to objects that are currently relevant to behavior. It is generally believed that the filtering of sensory information into higher level brain processes is regulated by top-down control signals in areas such as posterior parietal cortex (PPC). The goal of this proposal is to uncover the mechanisms of top- down attention employed by a subdivision of PPC, the lateral intraparietal area (LIP). A systems level neurophysiology approach will be taken to investigate the top-down interactions between LIP and an earlier ventral stream visual area, V4. Our first aim will utilize paired, simultaneous recordings in LIP and V4 to quantify the timecourse and magnitude of attentional modulation effects measured in the firing rate and local field potential (LFP) within each area and across areas. Several hypotheses will be tested concerning LIP's role in driving attentional modulation in V4, including the role of functional coupling between the two areas. The second aim will directly assess LIP's causal influence on V4 during selective visual attention using novel optogenetic techniques to silence/activate excitatory neurons in LIP. First, LIP will be momentarily silenced to remove top-down attentional feedback to V4 from LIP, directly suppressing attentional modulation of neural activity in V4 and impairing behavioral performance. Second, LIP will be activated so as to directly bias top- down attentional feedback toward a particular stimulus location while testing the resultant effects on associated V4 neurons, cross-area synchrony and behavior. An understanding of the neural basis of top-down attentional mechanisms in LIP will aid in developing a visual prosthesis to assist people with severe visual impairments. Furthermore, the ability to manipulate cells in the visual system at millisecond precision using optogenetics promises to significantly advance the capabilities of next-generation brain stimulators used in visual neural prostheses. PUBLIC HEALTH RELEVANCE: We expect that the successful implementation of this project will yield new insights into the mechanisms of top- down control of attention that will improve our understanding of central nervous system function in order to optimize the perceptual processing capabilities of people with low vision or blindness. Moreover, the use of novel optogenetic tools to probe attentional circuits by manipulating cells with millisecond precision will aid in the development of advanced neuro-stimulation approaches for visual prosthetics.